Method and system for controlled hyperthermia

ABSTRACT

Methods and for treatment of cancer and other diseases including complications from late stage viral infections by inducing hyperthermia in a patient relying on withdrawing blood from the patient and returning the withdrawn blood to the patient to establish an extracorporeal flow circuit. Blood is heated by passing through the extracorporeal circuit at a controlled rate until a target body core temperature in is achieved. Usually, the blood will be subjected to a continuously re-circulating dialysis to balance electrolytes. Additionally, the blood will be subjected to a continuously recirculating regeneration through a carbon sorbent column where toxins and contaminants are removed. The blood temperature is maintained at the target blood temperature for a treatment period, and the blood is cooled after the treatment period has been completed. The method can also be effective in treating rheumatoid arthritis, scleroderma, hepatitis, sepsis, the Epstein-Barr virus, and patients with life threatening complications from other viruses, including the COVID-19 virus. A method for removing viruses from the blood supply in an external circuit is also presented.

CROSS-REFERENCE TO RELATED APPLICATIONS

This divisional application claims priority from U.S. Provisional PatentApplication 62/840,438 “Method and System for Controlled Hyperthermia”and from U.S. Non-Provisional patent application Ser. No. 16/846,291Roger Vertrees “Method and System for Controlled Hyperthermia”. No newmatter is presented in this divisional patent application.

FEDERAL RESEARCH STATEMENT

None

FIELD OF THE INVENTION

The present invention relates generally to medical methods and devices.More particularly, the present invention relates to the extracorporealhyperthermic treatment of a patient's blood for the treatment of cancerand other diseases and conditions, including treatment of patients withlife threatening complications from viruses such as the COVID-19 virus.

BACKGROUND OF THE INVENTION

Hyperthermia has been well-accepted as a cancer treatment, particularlyfor solid tumors. The technique of regional perfusion and hyperthermiato treat localized malignancies in the limbs has been explored both withand without chemotherapy. Hyperthermia without accompanying chemotherapyhas been successful in treating refractory malignancies. A unique andinnovative method of hyperthermia to treat systemic diseases such asmetastatic cancers, rheumatoid arthritis, scleroderma, hepatitis,sepsis, the Epstein-Barr virus, and patients with life threateningcomplications from other viruses, including the COVID-19 virus, ispresented herein.

It would be desirable to provide improved methods and systems forsystemic hyperthermic treatment of patients with cancer and otherconditions. It would be particularly beneficial to provide such improvedsystems for systemic treatment to precisely raise the core bodytemperature to a desired target temperature by introducing aquantifiable and reproducible dose of extracorporeal heated blood whilereducing and counteracting any deleterious effects on the blood andpatient due to the necessary high temperature. At least some of theseobjectives will be met by the inventions described below.

DESCRIPTION OF THE PRIOR ART

-   Vertrees R A, Tao W, Pencil S D, Sites J P, Altoff D, Zwischenberger    J B: Induction of whole body hyperthermia with veno-venous    perfusion. ASAIO J 42:250-254, 1996;-   Alpard S K, Vertrees R A, Tao W, Deyo D J, Brunston Jr, R L,    Zwischenberger J B: Therapeutic hyperthermia. Perfusion 11: 425-435,    1996;-   Vertrees R A, Brunston R L Jr., Tao W, Deyo D J, Zwischenberger J B.    Parallel dialysis normalizes serum chemistries during veno-venous    perfusion-induced hyperthermia. ASAIO J 43(5):M806-811, 1997;-   Vertrees R A, Zwischenberger J B, Boor P J, Pencil S D. Oncogenic    RAS Results in increased cell kill due to defective thermoprotection    in lung cancer cells. Ann Thorac Surg 69:1675-80, 2000;-   Vertrees R A, Bidani A, Deyo D J, Tao W, Zwischenberger J B.    Veno-venous perfusion-induced systemic-hyperthermia: blood flow    redistribution and thermal gradients. Ann Thorac Surg 70:644-52,    2000;-   Vertrees R A, Deyo D J, Quast M, Wei G, Lightfoot K M, Boor P J,    Zwischenberger, J B. Development of human to murine orthotopic    xenotransplanted lung cancer model. J Invest Surg 13:1-10, 2000;-   Vertrees R A, Zwischenberger J B, Woodson L, Bedell E, Deyo D J and    Chernin J M. Veno-venous perfusion-induced systemic hyperthermia:    case report with perfusion considerations. Perfusion 16:243-248,    2001;-   Zwischenberger J B, Vertrees R A, Woodson L C, Alpard S K, Chernin J    M, Bedell E A. Veno-venous perfusion-induced systemic hyperthermia    percutaneous in advanced non-small cell lung cancer: initial    clinical experience. Ann Thorac Surg 72:234-42, 2001;-   Vertrees R A, Leeth A, Girouard M, Roach J, Kurusz, M,    Zwischenberger J B. Therapeutic whole-body hyperthermia: a review of    theory, design and application. Perfusion J. 17:279-290, 2002;-   Zwischenberger J B, Vertrees R A, Bedell E A, McQuitty C K, Chernin    J M and Woodson L C. Percutaneous venovenous Perfusion-Induced    systemic hyperthermia for lung cancer: a phase I safety study, Ann    Thorac Surg; 77:1916-1925, 2004-   He N, Li C, Zhang X, Sheng T, Chi S, Chen K, Wang Q, Vertrees R,    Logrono R, Xie J. Regulation of lung cancer cell growth and    invasiveness by Beta-TRCP. Mol Carcinog 42 (1): 18-28, 2005;-   Vertrees R A, Das G C, Coscio A M, Xie J, Zwischenberger J B, Boor    P J. A mechanism of hyperthermia-induced apoptosis in    RAS-transformed lung cells. Mol Carcinog 44:111-121, 2005;-   Vertrees R A, Das G C, Popov V L, Coscio A M, Goodwin T, Logrono R,    Zwischenberger J B, Boor P D. Synergistic interaction of    hyperthermia and gemcitabine in lung cancer. Cancer Biol Ther    4(10):1144-1153, 2005;-   Xu Y, Choi J, Hylander B, Kraybill W G, Repasky E A. Fever-range    whole body hyperthermia increases the number of perfused tumor blood    vessels and therapeutic efficacy of liposomally encapsulated    doxorubicin, International Journal of Hyperthermia, 2007;-   Vertrees R A, Zwischenberger J B, Boor P J, Popov V, McCarthy M,    Solley T N, Goodwin T. Cellular differentiation in three-dimensional    lung cell cultures. Cancer Biol Ther 7(3):404-412, 2008;-   Vertrees R A, McCarthy M, Solley T, Popov V, Roatin J, Pauley M, Wen    X, and Goodwin T: Development of a three-dimensional model of lung    cancer using cultured transformed cells. Cancer Biol Therap, 8(3):    345-356, 2009.-   Suvernev A V, Ivanov G V, Efremov A V, and Tchervov R: Whole Body    Hyperthermia at 43.5-44° C.: Dreams or Reality? Madame Curie    Bioscience Database [Internet], 2013.-   Fehr A R, Perlman S, Coronaviruses: An Overview of Their Replication    and Pathogenesis, Methods Mol Biol.; 1282: 1-23. 2015.-   U.S. Pat. No. 4,298,006 Systemic hyperthermia with improved    temperature sensing apparatus and method-   U.S. Pat. No. 5,391,142 Apparatus and method for the extracorporeal    treatment of the blood of a patient having a medical condition.-   U.S. Pat. No. 5,476,444 Specialized perfusion protocol for    whole-body hyperthermia-   U.S. Pat. No. 6,827,898 Hyperthermia method and apparatus. This    patent presents outdated methods of providing extracorporeal heating    to the patient's blood. Applicant's experience shows that the    temperatures contemplated in the '898 patent are far too high and    will most likely cause severe injury to the patient.-   U.S. Pat. No. 9,555,184 Systems and methods for treating blood.    Applicant contends that the method disclosed in this patent may be    unworkable and may lead to injury to patients.-   Hyperthermia in Cancer Treatment 1-800-4-CANCER Live Chat

The present invention builds upon the apparatuses, methods and analysispresented in much of the above prior art. The present inventionrepresents a significant increase in the treatment of advanced cancersand other diseases over the apparatuses and methods disclosed in theabove prior art.

SUMMARY OF THE INVENTION

The instant invention presents an improved system for treatment ofseveral types of diseases by means of strictly controlled hyperthermia.The improved system is referred to as the Hyperthermic Treatment System(HTS). Two specific configurations of the HTS are disclosed anddescribed herein—the Hyperthermic Extracorporeal Applied Tumor Therapy(HEATT) system which is used to treat cancer and the HyperthermicExtracorporeal Applied Virus Therapy (HEAVT) system which is used totreat patients with life threatening complications from COVID-19 andother viral infections. In addition, further configurations of the HTScan be used to treat other maladies.

Throughout this disclosure, reference is made to specific types ofequipment or apparatus such as the CardioQuip MCH-HT Modular CoolerHeater, the Medtronic HemoTherm Heat Exchanger and the REDY Regenerativedialysis sorbent system. These specific references to equipment andapparatuses are for ease of understanding. Similar existing or futureequipment and apparatuses that exhibit similar performancecharacteristics may be used.

All temperatures disclosed in this application assume proceduresperformed at or close to sea level. Target temperatures may need to beadjusted for procedures performed at higher elevations or under otherthan standard temperature and pressure conditions.

In the best mode, the system is configured as shown in FIG. 1. Ingeneral, there are two primary loops in the configured HyperthermicTreatment System (HTS): the main or primary loop and the heating loop.The main or primary loop is the treatment loop which comprises bloodflowing from the patient and being heated as it passes through the heatexchanger. The main or primary loop also is comprised of at least fourand preferably five pumps, the dialyzer, at least one sorbent column,and reservoirs containing intravenous (IV) fluids and electrolytesdesigned to ensure the blood chemistry is tightly controlled during thetreatment phase. The second or heating loop is a closed loop thatincludes the modular cooler heater and the heat exchanger. Water or someother heat exchange medium is heated in the modular cooler heater andpasses through the heat exchanger to heat the blood to the treatmentregime. It is vital that the heat exchanger be of high quality such asto allow no leakage between the water and the blood. Another vitalcomponent of the HTS is the Sensor Cable Management Box. Sensor leadsfrom the patient's body are attached to specific input portions of theCable Management Box. The data is then presented on a monitor. The datais monitored continuously. Based on the data, temperatures and flows areadjusted during the process.

The flow in the main loop is driven by the pumps. Pump #1 is the primarypump which pumps blood at between 1.0 and 3.0 liters per minute (LPM)from the patient, through the heat exchanger and back into the patient.Prior to reaching the heat exchanger, approximately 25% of the flow fromthe main loop is directed by Pump #2 into the Dialysis subloop and intothe Dialyzer. Pump #3 moves electrolytes from the upper and lowerdialysis reservoirs into the Dialyzer. Pump #4 moves fluid from theDialyzer through the sorbent column to remove impurities and back intoone of the dialysis reservoirs. Pump #5 moves IV fluid from the IVreservoir to the heat exchanger to ensure the volume of fluid remainswithin range.

In a first aspect of the present invention, a method for inducinghyperthermia in a patient comprises withdrawing blood from the patientand returning the withdrawn blood to the patient to establish anextracorporeal flow circuit, typically being either veno-venous,arterio-venous or veno-arterial. The blood is flowing between a rate of1.5 L/min to 3.0 L/min depending on patient size, heat transferrequirements, and other factors such as the patient's overall conditionand type of cancer. In a further refinement of the process, blood flowmay be controlled by the heat transfer rate where both temperature andblood flow rate are major factors. The blood is heated while passingthrough the extracorporeal circuit at a rate in the range from 0.05°C./min to 0.15° C./min (rate determined by formula) to a maximumtemperature of 48° C. by circulating water through a heat exchanger at amaximum temperature of 54° C. or until a target body core temperature(weighted average of indirect cerebral, esophageal, bladder, rectal andnasopharynx) is in the range from 41.8° C. to 42.2° C. (data collectedby Hall device) is achieved. The blood temperature is manipulated tomaintain the target tissue temperature for a treatment period in therange from 1 hour to 3 hours, and after the treatment period has ended,the blood is cooled until the body temperature has returned to 38° C. orbelow. Note that longer or shorter treatment periods can be utilizeddepending on the patient's size, stage of cancer, etc. The inventorshave found that optimum treatment is performed by rigorous adherence todosage control as determined by the amount of HTU's delivered to thepatient as defined below. In addition, the optimum temperatures andHTU's delivered will most likely be different for non-cancerousconditions such as Alzheimers or viral infections such as COVID-19. Theblood flow is such that approximately 150% (+/−25% depending ontreatment factors) of a patient's blood is processed through the HEATTsystem.

In a second aspect of the present invention, a method for inducinghyperthermia to treat a condition in a patient comprises withdrawingblood from the patient and returning the withdrawn blood to the patientto establish an extracorporeal flow circuit. The blood passing throughthe extracorporeal circuit is heated to raise the patient's body coretemperature to a target body core temperature. The rate of heating iscritically important. If the rate of heating is too slow then the cancercells can defeat it. If it is too fast, there is risk of vascularcollapse in the patient. The rate of heating is monitored in ‘real-time’and displayed. The rate of heating takes into consideration individualpatient size, blood flow rate and blood temperature. It is criticallyimportant to quantify the amount of heat delivered to the target tissue.We have developed, tested and verified for consistency andreproducibility a formula for determining a dose unit of heatdelivered—the hyperthermia treatment unit or HTU. One HTU is defined asthe amount of effective hyperthermic therapy delivered by maintaining amean core body temperature of 41° C. for one minute. This will allow formonitoring and comparing for safety and efficacy the effect of heat ontarget tissue. The target body core temperature is maintained for atreatment period in the range from 1 hour to 3 hours. Once temperaturedrops out of therapeutic range, the HTUs are determined. After thetreatment period has ended, the blood is cooled until the bodytemperature has returned to 38° C. or below. The blood is cooled byreducing the temperature of the water or other heat exchange mediumpassing through the heat exchanger. The rate of cooldown is important.If the cooldown is too fast or too slow, it could lead to adverseconsequences. The data indicates that a cooldown of 30 to 60 minutes isoptimal.

In a third aspect, the patient's blood is analyzed for acid-base balanceand anticoagulation status by withdrawing an aliquot of blood for eachassay. These elevated body temperatures will influence the acid-basebalance of patients due to an increase in solubility of gases atelevated temperatures and the increased metabolic rate that results fromthe high temperatures. Both facts must be taken into consideration inorder for patient survival and well-being. The blood is analyzed forboth oxygen and carbon dioxide levels as well as pH. These values arethen corrected for temperature at which they were collected by aproprietary formulae and necessary adjustments made in order to keepthese values within normal accepted ranges thus avoiding a significantacidosis. Additionally, the patient's blood is analyzed foranticoagulation. Many cancer patients have abnormal clotting profilesand since the changes in temperature (hyperthermia then cooling) altersthe metabolism of heparin, it is critical to monitor and amend theclotting status of these patients.

In a fourth aspect, the blood leaving the main pump (pump #1) is dividedinto two paths in different tubes, namely the main path and the lesserpath. Blood in the main path is pumped at approximately 2.5 L/minthrough the heat exchanger. Blood in the lesser path is pumped atbetween 15% and 35% (ideally 25%) of the flow rate of blood in the mainpath through the dialysis circuit. The lesser blood path pumps bloodinto the dialyzer in which it is divided into two components: (1) formedelements suspended in sera and (2) serum with dissolved salts. The seraand formed elements, once they leave the dialyzer, re-emerge with bloodat the heat exchanger. The sera/salt component is subjected to acontinuously recirculating circuit that goes through a carbon sorbentcolumn, into a dialysis holding chamber where it is re-constituted thenback through the dialyzer where a transfer of salts into the patient'sblood will occur. The blood is dialyzed to balance electrolytes andother serum solutes, and to introduce preselected salts selected totreat the particular condition. Dialyzing may comprise adding thepreselected salts to the dialysate during treatment based on the bloodanalysis and/or urine output, therefore an amount added may not berealized by the patient. Verthermia's proprietary formula accuratelypredicts the amount of an additive that is needed. Individualelectrolyte additions may be titrated in the dialysis flued and theninto the blood.

In a fifth aspect of the present invention, a method for inducinghyperthermia to treat a condition in a patient comprises withdrawingblood from the patient and returning the withdrawn blood to the patientto establish an extracorporeal flow circuit. The blood passing throughthe extracorporeal circuit is heated to raise the patient's body coretemperature to a target body core temperature. The target body coretemperature is maintained for a treatment period in the range from 1hour to 3 hours. However, the optimum delivery of cancer defeatingextracorporeal heating may be more closely dependent upon the number ofHTU's delivered and not necessarily the time. The blood is dialyzed witha dialysate to remove toxins and to introduce preselected salts selectedto treat the particular condition. The dialysate may be maintained in amain reservoir and recycled through a dialysis circuit including adialyzer that contacts the blood. One or more replacement reservoir(s)may be exchanged for the main reservoir after the dialysate in the mainreservoir is exhausted or for any other purpose. The replacementreservoir is preferably of identical construction and may become themain reservoir. A new replacement reservoir may be further exchanged forthe main reservoir after the dialysate in the replacement “main”reservoir becomes exhausted until the treatment period has ended. Afterthe treatment period has ended, the blood is cooled until the bodytemperature has returned to the target rest temperature of approximately38° C. (+/−1° C.). In an alternate embodiment, titration is controlledby proprietary Verthermia algorithms based on experiential data.Artificial intelligence based on the proprietary data algorithmscontrols the infusion pumps.

In a sixth aspect, the patient's blood that enters the dialyzer will beseparated into serum and a portion of serum plus larger formed elementsthat do not dialyze. The portion without formed elements in the serum isnow pumped through a sorbent column which may be composed of granularcarbon, glass beads, or similar material, either loose or affixed to amatrix. In an alternate embodiment, this process will remove toxins suchas tissue breakdown products as well as products of a disorderedmetabolism. The granular carbon is a nonselective filter and willcapture many different serum components. If glass beads are used, onlyspecific targeted molecules are removed. Once the ‘cleaned-serum’ exitsthe sorbent column it is recirculated back through the dialyzer in acontinuous circuit.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic flow diagram of the Hyperthermic Treatment System(HTS) 10 showing the various major components, including the modularcooler heater 200, the monitor 400, the cable management box 410, theheart lung machine 100, the heat exchanger 300, the dialyzer 450, thedialysate reservoirs 480 and 490, the charcoal sorbent column 460 andthe IV bag 550.

FIG. 2 is a closeup of the modular cooler heater 200.

FIG. 3 is the Cardio-Quip Monitor 400.

FIG. 4 is the cable management box 410.

FIG. 5 shows the connections leading from the cable management box tothe back of the monitor 400.

FIG. 6 is a closeup of the specially machined connectors 430.

FIG. 7 shows a standard heart lung machine 100.

FIG. 8 is the heat exchanger 300.

FIG. 9 is the dialyzer 450.

FIG. 10 shows the upper 490 and lower 480 dialysate reservoirs.

FIG. 11 is the charcoal sorbent column 460.

FIG. 12 is an exploded view of the dialysate reservoir 465

FIG. 12a is a closeup of the two stage filter 467 in each reservoir.

FIG. 13 shows the interior of the charcoal sorbent filter 472.

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the disclosed device, delivery system, andmethod will now be described with reference to the drawings. Nothing inthis detailed description is intended to imply that any component,feature, or step is essential to the invention.

A flow diagram for the Hyperthermic Treatment System (HTS) 10 of thepresent invention is provided in FIG. 1. Non-disposable components ofthe HTS include a standard heart-lung machine 100 FIG. 7 having four orfive pump heads. The main pump 110 on FIG. 1 moves the blood through theHTS circuit. A second pump 120 on FIG. 1 pumps blood through thedialysis circuit. A third pump 130 in FIG. 1 removes the dialysis fluidfrom the main dialysis reservoir and pumps it through the dialyzer 450.A fourth pump 140 in FIG. 1 draws the dialysis fluid out of the dialyzerand pumps it through the carbon sorbent column and into the bottom maindialysis reservoir. An optional fifth pump 150 in FIG. 1 is used to giveadditional volume into the circuit when needed.

A modular cooler heater such as a CardioQuip MCH-HT or similar device200 in FIG. 2 is used to pump hot and/or cold water into the heatexchanger 300 in FIG. 1. The water temperature and the rate of waterflow are both manually controlled by the operator. However, they couldalternatively be automatically controlled in other embodiments. All theinformation is displayed on a CardioQuip HT-monitor or similar device400 (FIG. 3). Displayed data include all temperatures, pressures andflows as well as the rate of heating, HTUs and all critical time values.Most of the data can be shown in graphical form allowing one to assessthe time-course as well as the discrete value.

In the best mode, a perfusionist monitors and adjusts the heating andblood flow. A Nephrologist/dialysis tech monitors and adjusts levels ofelectrolytes.

A sensor cable management box 410 (FIG. 4) is another piece ofnon-disposable equipment and serves as both a directory of which channelto use for what temperature and as a collection point for these manynon-sterile cables. As can be seen in FIG. 4, the sensors on the patientare plugged into the illustrated anatomical locations shown on a side ofthe box. Therefore, the chance of connecting specific temperature orother sensors to the wrong input on the monitor/controller issignificantly reduced. The sensor cable management box and all othertemperature cables and pressure transducers (from the extracorporealcomponents of the HTS) connect to the pump controller throughconnections on the back of the monitor 475 (FIG. 5).

Non-disposable stainless-steel connectors 430 that are critical tomaking this circuit functional are shown in FIG. 6. These connectors arespecially machined to specific tolerances for the HEATT procedure. Theconnectors are typically made of stainless steel or similar metals oralloys due to their ability to retain heat. Suitable plastics may bedetermined to replace metallic connectors.

Circuit Orientation and Disposable Components

The extracorporeal circuit includes the HTS and is assembled in asterile manner. Briefly, small diameter tubing, nominally ⅜-inch tubing,will be connected to a small diameter cannula, nominally a 15 Fr.cannula placed in the jugular, femoral or other suitable vein, and bloodwill be aspirated through the cannula by pump #1. Once through the pump,the blood divides into two separate parallel blood paths with thegreater amount of the blood going directly into the heat exchanger suchas a Medtronic HemoTherm Heat Exchanger or similar device 300 shown inFIG. 8 and displayed in the flow diagram FIG. 1. Main pump #1 110 flowis up to 1.5 Liters Per Minute (LPM) with about 25% diverted into thedialyzer 450. The heat exchanger 300 is connected to the MCH-HT 200which circulates water or another heat exchange medium through the heatexchanger to control the temperature of the blood. The dialysis circuitpump (pump head #2) directs blood along the lesser blood path throughthe dialyzer 450 (FIG. 9) and back into the main blood stream where itthen goes into the heat exchanger. Once the blood leaves the heatexchanger, the blood flows through an arterial blood filter and throughsmall diameter tubing (nominally ¼ inch tubing) into a small diametercannula (nominally a 13 Fr. Cannula) and into the patient's vena cavathrough the jugular or femoral vein.

With pump head #3 130 running about 10% slower than pump head #4 140,the dialysis fluid is aspirated from the lower dialysis holdingreservoir and propelled into the dialyzer 450. Pump head #4 140aspirates dialysis fluid from the opposite end of the dialyzer andpropels it into a charcoal sorbent column 460 (FIG. 11) and into thelower dialysis main reservoir. Dialysis flow is countercurrent to bloodflow through the dialyzer. Control of electrolyte salt concentrations isaccomplished by altering the flow rates from the electrolyte-enhanced IVbags 470 manifolded and connected to a top of either the lower or maindialysate reservoir 480 or upper or secondary dialysate reservoir 490. Adialysis solution (bath) is located in a main (nominally the lower)dialysate reservoir 480 (FIG. 10) and dialysis enhancements in new bathsolution is located in the upper or secondary reservoir. In a furtherrefinement of the current embodiment of the instant invention, the upperreservoir is eliminated.

Recirculating Dialysis Circuit

In the instant invention, a dialyzer 450 is used to separate and isolatea portion of the sera from formed elements in the blood (red and whiteblood cells, platelets and other components greater in size thanapproximately 50,000 daltons). The separated sera (plasma water withsalts and other solutes smaller than approximately 50,000 daltons insize) is then passed through a carbon sorbent or glass bead column 460to remove contaminants and then through the dialysis holding chamberwhere reconstitution of the plasma water occurs. Dialysis may beaccomplished using a modified regenerative dialysis sorbent dialysismachine (such as the REDY system) or by adapting other conventionaldialysis circuits to existing heart-lung pumps. In adapting a REDYsorbent recirculating dialyzer and carbon column to this application,the instant invention uses a unique dialysate reservoir 465 (FIG. 12).The reservoir has a simple design. Two reservoirs 480 and 490 areemployed in each HTS circuit (FIG. 1 and FIG. 10). An upper or secondaryreservoir 490 serves as a holding chamber where new dialysis is held andaltered to the desired concentration of serum electrolytes. A lower ormain reservoir 480 is the main reservoir which provides the dialysatenecessary for continuous recirculation. Conveniently, both reservoirsmay have the same design and will include multiple ports on top with asingle outlet port on the bottom. A cap on top is removable to allow aquick exchange of solutions. Each reservoir has inside a two-stagefilter 467 (FIG. 12a ). An inner layer may be a gross filter and anouter may be a finer one. The purpose of these filters is to removeparticulate contaminants that could potentially enter and damage thehollow-fiber dialyzer.

Continuous Recirculating Liver Detoxification Portion of Circuit

A conventional REDY charcoal sorbent filter or similar device has beenmodified to perform ‘liver detoxification’ of the recirculatingdialysate for the HTS. The charcoal portion acts to detoxify the serumcomponent of the blood. The dialysis separates blood components based onsize excluding serum solutes larger than 50 kilodaltons (kDa) frompassing into the recirculating bath solution. This solute/bath solutionthen passes through the charcoal where ‘liver detoxification’ occurs. Aconventional REDY sorbent column may include items which are notnecessary for the HTS. In particular, a conventional REDY sorbent columncontains chemicals that remove anions and cations from the bloodrequiring the HTS to replace these ions in the recirculating bathsolution. A modified charcoal sorbent filter suitable for HTS includes amain body of the filter 472 (FIG. 13) that is the container for thecharcoal. A second portion attaches to the base and may containchemicals and/or other components that will remove specific toxin(s)that can be more efficiently removed by a chemical or other component.These two portions may be removably connected by a screw connection,some bayonet type connections, or other known fastening mechanisms.

Set-Up and Priming

The HTS circuit is assembled in a sterile manner prior to the procedure.The apparatus is primed by a three-step process.

Step 1 comprises using approximately one liter of Plasmalyte A to whichapproximately 2,500 U heparin and approximately one ampule of sodiumbicarbonate has been added is used to ‘wash out’ the heating portion andblood side of the dialyzer in the circuit and to displace as much air aspossible. The dialysis-side of the dialyzer is prevented from priming atthis point. Additionally, this prime fluid is heated to approximately38° C.Step 2 comprises requiring approximately two liters of heparinizedPlasmalyte A to completely fill and de-air the dialysis side whichincludes the carbon sorbent or glass bead column. Since there is noheater in this portion of the circuit, there will be no heating in thisportion of the prime. At the interface of the dialysis and heatingcircuits within the dialyzer, micro-air bubbles will form and be visiblein the circuit. These bubbles must be eliminated at this stage which isaccomplished by running both circuits simultaneously for about 30minutes at about 38° C.Step 3 occurs once the air has been removed and it appears theHyperthermic Extracorporeal Applied Tumor Therapy (HEATT) perfusion willbegin in about 15-minutes; the heating side prime bag is replaced with afresh 1-liter bag of Plasmalyte-A, approximately 2500 U of heparin,approximately one ampule of sodium bicarbonate and approximately 50 mLof approximately 25% human serum albumin and allowed to recirculatethrough the entire circuit at approximately 38° C. perfusate temperaturethus ‘coating’ the entire Core HFC circuit. This bag will then beremoved from the prime bag connector and attached to the IV bag 550connector for pump #5 150 and given as-needed to maintain patient-pumpcirculating volume.Patient Connections

Pre-operatively in the pre-operative holding unit the patient receivedapproximately 250 mL of a steroid that prevents the release ofsubstances in the body that cause inflammation, such as Solu-Medrol,approximately 100 mg of thiamine, approximately 1 gram of ananti-seizure drug such as Keppra and an IV of normal saline withapproximately 20 milliequivalents of KCl at approximately 200 mL perhour. In the operating room, anesthesia is induced with propofol,isoflurane, and sufentanyl. Blood is collected for baseline studiesincluding being tested for anticoagulation properties. Patients receivea systemic dose (approximately 3 mg/Kg of body weight) of heparin(preferably beef lung heparin) prior to cannulation injected into thecentral line at the start of the procedure, and additional heparin orfresh frozen plasma administered whenever the Activated Clotting Time(ACT) is below 500 seconds (5 times baseline). Additionally, patientshave intravenous drips of vasopressin, neosynephrine, CaCl₂, MgSO₄,NaPO₄, KCl, and NaHCO₃. After induction of anesthesia, patients areinstrumented with an approximately 18-gauge radial artery catheter formonitoring arterial pressures and collection of arterial blood. Acentral line is placed to measure the central venous pressure and forthe administration of supplemental fluids. Temperature probes wereinserted into both auditory canals and connected to Ports 1 and 2 of theSensor cable management box 410 (FIG. 4). A urinary bladder drainagecatheter with integral temperature probe is inserted into the bladderand connected to a collection bag with the temperature connected to Port4 of the Sensor cable management box 410 (FIG. 4). A rectal temperatureprobe is placed and connected to Port 5 of the Sensor cable managementbox. An approximately 13 Fr. by approximately 15 cm long Maquet cannulaor similar cannula is inserted into the right internal jugular vein andadvanced into the vena cava at the level of the right atrium and heparinlocked. An approximately 15 Fr. by approximately 50 cm long Medtroniccannula or similar cannula is inserted into the right femoral vein,advanced into the distil vena cava and heparin locked. Anothertemperature probe is placed into the nasal-pharynx and connected to Port3 of the Sensor cable management box and another temperature is insertedthrough the mouth and placed within the nasopharynx and connected toPort 6 of the Sensor cable management box. A sheet of aluminized Mylar®or similar material will be wrapped around the patient and tubes tominimize heat loss (optional dependent on patient temperature).

HTS Operations

Pre-mixing Phase. Upon completion of all cannula insertion, the cannulais connected to the extra-corporeal circuit and perfusion begun. Thepurpose of this phase is to establish, integrate and coordinate theHEATT perfusion, dialysis and the liver detoxification circuits toachieve optimal flow rates in each sector and to assure that allmeasured pressures and flows are within expected limits. The main bloodpump flow should increase in approximately 500 mL aliquots over anapproximately five minute period while observing pressures (patient andcircuit) and temperatures. The three pressures measured are (1) theblood into the patient which should not exceed 300 mmHg, (2) blood outof the patient which should not be more negative than −100 mmHg and (3)the pressure drop across the charcoal sorbent or glass bead column whichshould be less than 400 mmHg. Additionally, circuit integrity should beassessed for water, blood or air leaks. The time spent in this phasevaries from 5 to 10 minutes depending on the patient's response toperfusion. Since this is a veno-venous circuit, increasing blood flowmust be done very slowly so as to not deplete CO₂ returning to the lungsand furthermore to not overwhelm the right side of the heart with adiluted blood volume. Optimal blood flow is patient dependent but shouldrange about 20 to 30 mL/kg/min with a maximum flow of about 1500 mL/min.

Control of Dialysis

Blood chemistries are analyzed on an approximately 15-minute basis; theresults of these analyses allow for a prompt and accurate alteration ofthe serum electrolytes back to normal physiological limits. Dialysisflow through pump #2 120 is started as soon after the initiation ofperfusion as is possible and generally when main blood flow is about 1liter/min. Pump #2 (dialysis pump) is adjusted to run at about 25% ofthe main blood pump and at this phase will be about 250 mL/min. Thispump can operate with both dialysis bath in and out pumps off and theirconnections to the dialyzer clamped off. When these pumps are started,and the clamps removed the inflow pump to the dialyzer runs at a rateapproximately 10% slower than the outflow pump; resulting in theproduction of an ultrafiltrate. If these pumps are operated in thereverse manner with the inflow less than the outflow, the bath solutionwill be delivered into the patient with the potential of “unloading”dialyzer-bound substances back into the patient. The dialysis bathsolution or dialysate is a recirculating system throughout the entireprocedure. The starting dialysate solution includes approximately 1liter of normal saline to which approximately 5 milliequivalent (mEq) ofpotassium, approximately 40 mEq of sodium bicarbonate and approximately4.5 mEq of calcium chloride has been added. A matching infusatecontinuously replenishes the dialysate bath and runs at approximately 80cc/hr. When the bath becomes diluted by approximately 10% from themandated ultrafiltration, the infusate is increased to approximately 100cc/hr. At approximately 20% dilution, the bath solution is replaced witha new fresh solution and the infusate rate reduced back to approximately80 cc/hr.

Should the blood chemistry analysis indicate that the patient has a lowserum potassium level (approximately 10% drop in value), then thedialysate is changed from 4 to 6 mEq: an additional drop ofapproximately 10% in the serum potassium causes the start of anadditional infusate of approximately 100 mEq KCL/250 cc D5W (5% Dextrosein water) given through a central vein at approximately 50 cc/hr. If thepotassium is still outside the normal range, the dialysate bath isincreased by approximately 1 mEq and the infusate is increased byapproximately 25 cc/hr.

Should the blood chemistry analysis show a low calcium level (decreaseof approximately 10%), then a central drip infusate of approximately8-grams of CaCl in approximately 500 cc D5W at approximately 100 cc/hris started. For every approximately 5% drop in the serum calcium levelbelow target range, there is an increase in the infusate rate byapproximately 50% more than the previous rate. If the calcium level istoo high, the dialysate bath is changed to an approximately 3-mEq bathfrom the prior approximately 4-mEq bath and the infusate is decreased toapproximately 50 cc/hr.

Should the blood chemistry analysis show a low pH (acidosis), aninfusate, composed of approximately 400 mEq NaHCO3/LDSW, is started at arate of approximately 100 cc./hr. For every approximately 5% drop in pHfrom the target level, the infusate rate is increased by approximately50 cc./hr. If the correction of the pH is not reached with the abovechange in the infusate rate, then the rate is increased by approximately100 cc/hr from the baseline rate.

Should the blood chemistry analysis show a low serum phosphorus, aninfusate of NaHPO4 approximately 90 mMOL/LDSW is started atapproximately 100 cc/hr. For a serum phosphorus level less than3.5-mg/100 cc, the infusate rate is increased by approximately 25% fromthe previous rate. If the serum phosphorus is still not normalized, theinfusate rate is increased by approximately 50% from the previous rate.For a serum phosphorus greater than 5 mg/100 cc, the infusate rate isdecreased by approximately 25% from the previous rate. If the serumphosphorus is still elevated, then the infusate rate is further decreaseby approximately 50% from the previous rate.

Control of Liver Detoxification

Control of liver detoxification is accomplished in the sorbent columnand is a function of mass transfer. The more of the dialysis solutionthat is exposed to the charcoal or glass beads, the more toxin isremoved. Therefore, this is flow dependent. To remove more toxins, theflow through the carbon needs to be increased. The limiting factor hereis the pressure drop across the charcoal or glass bead sorbent columnwhich should not exceed 400 mmHg.

Mixing Phase

Blood samples are obtained at least every 15 minutes during theprocedure, or when otherwise clinically indicated. Temperatures will bemonitored and recorded at the following sites: deep esophagus, right andleft tympanic membranes, rectum, bladder, and nasopharynx. The averagecore temperature (Tc) is defined as the mean value of the esophagus,right and left auditory canals, rectum, nasal-pharyngeal, and bladdertemperatures. The patient will be allowed to stabilize for approximately15 minutes on veno-venous bypass at approximately 38° C. prior tostarting the heating phase. This also allows establishing a hemodynamicand metabolic baseline for that individual. Once main blood flow hasbeen established, the dialysis pump (#2) will be adjusted to divertapproximately 25% of the blood into the dialysis circuit. Both dialysisbath pumps should not exceed approximately 50% of pump #2 flow. Thepurpose of this phase is to equilibrate the patient's temperature to thecircuit temperature before starting to heat as this will give us clearerbaseline chemistry values. After the 15-minute interval is completed,the heating phase begins.

Heating Phase

The specialized CardioQuip Heater Cooler or similar device will beengaged to heat the blood to reach therapeutic hyperthermia interval(T6=42° C.). A water-to-blood temperature gradient will be maintainedbelow approximately 10° C. The device has been customized to not exceeda maximum water bath temperature of 52° C. (and a maximum bloodtemperature of 48° C.). A proprietary formula has been developed that iscalled “the heating rate” which calculates heat transfer and then makesa prediction going forward. If the prediction falls outside the limits,then an alarm will indicate that heating is either too fast or too slow.Currently, our standard is set at 0.1° C./minute±1.2 SD. As the averagecore temperature approaches approximately 42° C., attention must bedirected to the auditory canal temperatures as these temperatures shouldnot exceed 42.2° C. As the average core temperature exceeds 40.8° C.,another formula called hyperthermic therapy units (HTUs) is called intoplay. This formula calculates the amount of heat that the body isreceiving in real-time and is equivalent to a ‘dose of heat.’ Once theaverage core temperature reaches 42° C., water bath temperature will bereduced in stages such that the target temperature of approximately 42°C. is maintained. When water-bath temperature is in the range of 44° C.,a reduction in blood flow will help to reduce the amount of heatdelivered to the patient. The final set of mathematical relationshipsemployed is for the temperature correction of the blood gases and pH.Blood gas analyzers measure oxygen, carbon dioxide and pH atapproximately 37° C. regardless of the temperature at which the bloodwas collected. Since the solubility of gases in solution is dependentupon the temperature of the solution, this results in the need to derivethe ‘true’ value for these variables. These calculations are applied toboth arterial (collected at the radial artery) and venous blood (bloodout of patient to pump) gas results once hyperthermia is initiated untilthe body core temperature returns to normal. Although there are manydifferent forms of these equations, we have found that the followingrelationships work well. With increasing temperature, more CO₂ isretained by the blood resulting in a respiratory acidosis. The partialpressure of CO₂ (pCO₂) of the patient at the elevated temperature can befound by adding approximately 2-mmHg for each degree above 37° C. to thepCO₂ measured by the machine. The partial pressure of O₂ (pO₂) of thepatient at the elevated temperature can be found by adding approximately5 mm Hg for each degree above 37° C., and the pH can be found bysubtracting approximately 0.015 pH units for each ° C. above 37° C.

Therapeutic Phase

This phase starts once the target temperature of 42.0±0.2° C. has beenreached as determined by the average core calculations and it will bemaintained for approximately 120 minutes. Not all temperatures will beat 42° C. at the start of the therapeutic interval and some may neverreach 42° C. at all. This is often more of a problem with thetemperature probe than with the site not getting hot enough.

Pump Orientation

The following information must be displayed and monitored on acontinuous basis as is shown above:

-   -   (1) flow rate in LPM for all three pumps, for example, 0.78 for        the main (i.e. Pump #1), 0.34 for the dialysis pump (pump #2),        and 0.20 and 0.19 for the dialysis bath pumps (pumps #3 and #4).    -   (2) MCH data of 45° C. with a water set point of 45.1° C.    -   (3) System pressures in the upper right corner showing a patient        inflow pressure of 27, outflow of 0 and a dialysis sorbent        pressure of 375 mmHg.    -   (4) On the right side of the monitor are the various temperature        readings starting with heat exchanger in water temperature        (HtExIn), heat exchanger water out, patient blood temperature        out (PtBldOut), patient blood in temperature, then all the body        temperatures. The mean is calculated continuously.    -   (5) Across the bottom are three clocks showing total pump time,        heating time and therapy time.    -   (6) Immediately above the clocks is the output from the heating        rate formulae expressed as overall and current, and the HTUs        (128.30).    -   (7) In the center of the screen is a graphic representation of        the time-course for each measured temperature. This is        particularly useful during the heat up and cool down phases. If        the main pump flow has been decreased during this period,        starting at about 110 minutes return the flow to the optimal for        that patient which should be about 1500 mL/min. This higher flow        rate will be needed in order to effectively cool the patient        however too high a flow rate encourages veno-venous shunting        resulting in insufficient cooling. This information and data is        continuously monitored by the Perfusionist.        Cooling, De-Cannulation and Discontinuation of HEATT Procedure.

After approximately 120 minutes at the target temperature oralternatively when the prescribed number of HTU's is administered, thewater set temperature is reduced to approximately 38° C. The gradientbetween the patient blood out temperature and the heat exchanger waterin temperature must be carefully observed and monitored as this gradientis critical. Once this gradient is gone, the water set temperature isreduced to approximately 35° C. Perfusion can be discontinued once theaverage core temperature and patient blood outlet temperatures arestable at approximately 38° C. Once the perfusion is complete, theresidual volume in the perfusion circuit will be returned to thepatient. Next, cannulae will be removed, heparin will be reversed withprotamine and cannulation sites closed and verified that no bleeding isoccurring. ACT should be about 120±20 seconds and a heparin: protaminetitration can be done to verify that all the heparin has beenneutralized.

Aside from the patient's maximum core body temperature, the mostcritical component of a hyperthermic procedure is the rate of increasein core body temperature. For patient safety, therefore, the heatingrate must be monitored closely. Previous studies have shown thatthermoresistance can be manifest within about 200 minutes. Therefore,one needs to be at the therapeutic temperature by this time. (Henle, K Jand Roti Roti, J L, Radiat Res 82, 138-145, 1980). A core bodytemperature increase of 0.25° C./min may be fatal, whereas heating athalf that rate, or ˜0.12° C./min, is safe.

The HEATT device uses the patient's mean core body temperature tocalculate the overall rate of heating, which is found by subtracting theinitial temperature To from the current temperature T_(i) and dividingby the total elapsed time in minutes. The device also calculates thecurrent rate of heating, which is found by subtracting the temperaturethree minutes in the past Ti−3 from the current temperature Ti anddividing the result by 3. A heating rate more than 0.12° C./min triggersan alarm. Other pre-alarm setpoints may be instituted to warn thePerfusionist that the heating rate alarm limit is approaching.

Overall and Current Heat Rate

T_(o)=Patient's initial temperature.

T_(i)=Patient's current temperature

T_(i-3)=Patient's temperature three minutes earlier.

t_(tot)=Total elapsed heating time

OHR=Overall Heat Rate

CHR=Current Heat Rate

${OHR} = \left( \frac{T_{i} - T_{o}}{t_{tot}} \right)$${CHR} = \left( \frac{T_{i} - T_{i - 3}}{3} \right)$

One of the unresolved challenges in hyperthermic treatment is theability to quantify a particular “dosage” of hyperthermia. Measuring theactual amount of energy added to the patient is not helpful becausevariances in patient physiology and environmental conditions have asignificant impact on the energy required to deliver effectivehyperthermic treatment. Ultimately, though, the only criticalmeasurement is the actual core body temperature. If the core temperatureis correct, therapy occurs. Other factors are essentially irrelevant.Therefore, a new unit has been developed: the HTU, or HyperthermicTreatment Unit. One HTU is defined as the amount of effectivehyperthermic therapy delivered by maintaining a mean core bodytemperature of 41° C. for one minute.

Because effective therapy begins at a minimum temperature (T_(min)),calculations of HTU delivery are only valid when the instantaneoustemperature T_(i) is at or above T_(min), T_(min) is dependent upon theparticular disease being treated.

Based on the therapy effect vs. temperature curves (Vertrees R A,Brunston R L Jr., Tao W, Deyo D J, Zwischenberger J B), paralleldialysis normalizes serum chemistries during veno-venousperfusion-induced hyperthermia. ASAIO J 43(5):M806-811, 1997), theeffective therapy increases in an approximately 2× linear fashionbetween 41-43°, with therapy delivered at 43° C. being three times aseffective as at 41° C. The hyperthermic therapy H being delivered duringtime interval i is thus calculated as:T_(i)≥T_(min)Where:

1. t_(i) and t_(i-1) are times in minutes.

2. T_(i) and T_(min) are temperatures in ° C.

3. H_(i) is the number of HTU's delivered in a given incremental timeinterval.

4. H_(T) is the total number of HTU's delivered to the patient duringthe treatment period.

$H_{i} = \left( {1 + {\left( {T_{i} - {41}} \right)\left( \frac{t_{i} - t_{i - 1}}{60} \right)}} \right.$For example, the number of HTUs delivered in a three second timeinterval during which the mean core temperature is 41.5° C. iscalculated as:

$H_{i} = \left( {{1 + {\left( {{4{1.5}} - {41}} \right)\left( \frac{3}{60} \right)}} = {0.075}} \right.$The total number of HTU's delivered to the patient is the sum of theincremental values.

$H_{T} = {\sum\limits_{i = 1}^{n}H_{i}}$Treatment of Late Stage COVID-19 Virus Infection

A modification of the HEATT method (Hyperthermic Extracorporeal AppliedVirus Therapy [HEAVT]) has been shown to be effective for treatingpatients with life threatening complications from COVID-19 and otherviral infections. In general, the treatment for late stage COVID-19patients is similar to treatment of cancer patients with the notableexceptions of (1) limiting the upper range of temperature toapproximately 40° C. and (2) modifying the procedure to include anoxygenator, given the fact that most patients would be in respiratoryfailure. Treatment is performed for approximately two hours or until asuitable amount of HTU's is applied to the patient.

The two hour duration at or about at the upper range temperature exposesapproximately 150% of the patient's blood volume to both the heat andhemodiaultrafiltration. Understanding that these patients are inrespiratory failure, an oxygenator can be introduced into this circuitthus oxygenating and removing carbon dioxide. Veno-venous perfusion withan oxygenator is a commonly used perfusion technique to support patientsin respiratory failure which is referred to as the ExtracorporealMembrane Oxygenation (ECMO) process. After the approximately two hoursof heating, the patient will be returned to a normothermic state andwill continue to be supported with veno-venous ECMO until the patientcan be weaned from it as determined by their respiratory status. Thehemodiaultrafiltration will be switched over to continuous veno-venoushemofiltration (CVVH) thus allowing for removal of residualproinflammatory acute-phase cytokines.

CVVH (Continuous Veno-Venus Hemofiltration) is a process where adialysis catheter is placed in one of the main veins of the body. Thiscatheter has two separate lines. Blood flows out of the catheter andinto the CVVH machine, which then goes into a filter where waste fluidis taken off. Fluids and electrolytes (i.e. sodium and potassium) arethen replaced. Finally, the blood is returned back to the patientthrough the catheter. In addition, large molecules are removedincluding, but not limited to, pro-inflammatory cytokines. This can havepositive clinical impact where the inflammatory process plays a strongclinical role. For example: In the article “Immunomodulatory Effect ofContinuous Venovenus Hemofiltration during Sepsis”, (Giuseppe Servillo,Maria Vargas, Antonio Pastore, Alfredo Procino, Michele Iannuzzi,Alfredo Capuano, Andrea Memoli, Eleonora Riccio, and Bruno Memoli BiomedRes Int. 2013; 2013: 108951. Published online 2013 Jul. 23. doi:10.1155/2013/108951) it was shown that CVVH removes the pro-inflammatorycytokine mediator Il-6 with positive clinical results. This was alsoconfirmed in several recent articles. In an article published in theJournal Frontiers Immunol. January 2019 “On the Effects of Changes inthe Level of Damage Associated Molecular Patterns Following CVVH Therapyon Outcomes on Acute Injury Patients with Sepsis”, it was shown thatthere was a significant reduction in the levels of circulating Il-6,TNF, and DAMP (damage associated molecular patterns such as:Mitochodrial DNA, Nuclear DNA, and Heat Shock Proteins), also withpositive clinical results. This is just an example of two of manyarticles published stating that CVVH may have a positive impact ondiseases by employing pro-inflammatory cytokine reduction.

Upon discontinuation of this procedure, an upregulation of the immunesystem in cancer patients has been shown and is expected to occur in thechronic phase of COVID-19 also as the immune system begins to recognizethe presence of the foreign glycoproteins.

In another alternate embodiment of the present invention, blood from theblood supply can be heated in an external circuit to eliminate viruses,including the COVID-19 virus. Implementing such a method can ensure thatblood that was donated by a person who was infected with a virus, butwho was asymptomatic when the blood was donated, can be cleansed of avirus. Normally red cells are stored for up to six weeks (forty-twodays) before they are disposed of. If present, the virus would mostlikely reside in the red cells. This would present ample opportunity foran infected, yet asymptomatic, person to donate blood and eventuallyhave that infected blood infect another person during surgery. Thisembodiment of the instant invention presents a methodology for avoidingthe same type of spread of viruses through surgery, transfusions, etc.that occurred during the AIDS epidemic.

Whereas the best mode for the present invention involves establishing anextracorporeal circuit that necessarily included the patient, in thisalternate embodiment, blood from the blood supply that may have beeninfected is introduced into a stand-alone circuit. The blood should beslowly heated in a dynamic circuit from its normal storage temperatureof about 6° C. to a treatment range of 40° C. to 49° C. and preferably45° C. to 47° C. for a period of 10 to 40 minutes and preferably 15 to30 minutes. All normal precautions exercised during treatment andhandling of blood should be exercised in order to ensure that the bloodis not damaged. Following treatment, the blood should be cooled to roomtemperature and then stored at the normal storage temperature of about6° C.

The blood is heated and cooled using a modular cooler heater (MCH) orsimilar device. Blood chemistry is monitored throughout to ensure theblood is not damaged and to further ensure that blood chemistry remainswith acceptable levels.

What is claimed is:
 1. A method for inducing hyperthermia to treat acondition in a patient, said method comprising: a. withdrawing bloodfrom the patient and returning the withdrawn blood to the patient toestablish an extracorporeal flow circuit; b. heating blood passingthrough the extracorporeal circuit to raise the patient's body coretemperature to a target body core temperature; c. controlling the rateof heating and blood flow to within defined limits; d. maintaining thetarget body core temperature for a treatment period in the range from 1hour to 3 hours; e. analyzing blood for both oxygen and carbon dioxidelevels, as well as pH, and correcting the above levels for temperature;f. dialyzing the blood in a dialyzer and dialysis circuit to introducepreselected salts selected to treat the metabolic condition; g. movingthe blood throughout the extracorporeal flow circuit by means of up tofive pumps connected to a heart lung machine, wherein the five pumpsfurther comprise a main pump (#1), a dialysis pump (#2), two dialysisbath pumps (#3 and #4), and an optional IV fluids pump (#5); h.detoxifying the blood by continuously passing it through a charcoal orglass bead sorbent column; and i. after the treatment period has ended,cooling the blood until the body temperature has returned to 38° C. orbelow.
 2. A method as in claim 1 where the blood from pump #1 is splitinto two paths, wherein one path continues into the heat exchanger andthe second path travels through the dialysis circuit.
 3. A method as inclaim 1 where the blood from pump #1 is split into two paths, whereinone path continues into the heat exchanger and the second path travelsthrough the dialysis circuit at between 15% and 35% of the flow rate ofthe first path.
 4. A method as in claim 1 where the blood that entersthe dialyzer is separated into serum and a portion of serum plus largerformed elements that do not dialyze.
 5. A method as in claim 1 wherepump #3 operates approximately 10% slower than pump #4.
 6. A method asin claim 1 where dialysis fluid is aspirated from a lower dialysisholding reservoir and propelled into the dialyzer.
 7. A method as inclaim 1 where pump #4 aspirates dialysis fluid from the dialyzer andpropels it into the sorbent column and then into a lower dialysisholding reservoir.
 8. A method as in claim 1 where control ofelectrolyte salt concentrations is accomplished by altering the flowrates from a series of electrolyte-enhanced IV bags manifolded andconnected to a top of either a lower dialysate reservoir or an upperdialysate reservoir.